Rauhut-Currier Research Articles

Highly enantioselective intramolecular Rauhut–Currier reaction catalyzed by chiral thiourea–phosphine

A highly enantioselective intramolecular Rauhut–Currier reaction of bis(enones) has been developed by employing bifunctional thiourea–phosphine organocatalysts based on a chiral cyclohexane scaffold. In the presence of 10mol% of thiourea–phosphine 1h, the desired products were obtained in good yields with up to 99% ee.

Enantioselective Intermolecular Cross Rauhut–Currier Reaction

Enantioselective Intermolecular Cross Rauhut–Currier Reaction

Intramolecular Morita–Baylis–Hillman and Rauhut–Currier reactions. A catalytic and atom economic route for carbocycles and heterocycles

Intramolecular MBH and RC reactions: glorious past and future opportunities.

Highly enantioselective intermolecular cross Rauhut-Currier reaction catalyzed by a multifunctional Lewis base catalyst.

The highly enantioselective intermolecular cross Rauhut-Currier reaction of different active olefins catalyzed by a multifunctional chiral Lewis base was reported. The RC products were obtained in excellent yields (up to 98 %), high chemo- and enantioselectivity (up to 96 % ee). The reaction could be performed on a gram scale using 1 mol % of the multifunctional phosphine catalyst.

Highly Enantioselective Intermolecular Cross Rauhut-Currier Reaction Catalyzed by a Multifunctional Lewis Base Catalyst

The highly enantioselective intermolecular cross Rauhut–Currier reaction of different active olefins catalyzed by a multifunctional chiral Lewis base was reported. The RC products were obtained in excellent yields (up to 98 %), high chemo- and enantioselectivity (up to 96 % ee). The reaction could be performed on a gram scale using 1 mol % of the multifunctional phosphine catalyst.

A catalytic approach to the MH-031 lactone: application to the synthesis of geralcin analogs

A concise, 5-step synthesis of the hepatoprotective lactone MH-031 was achieved. Our approach utilizes several catalytic processes, namely, a Rauhut–Currier reaction, a chemoselective Fisher esterification, and a ring closing metathesis. Further elaboration of this lactone yielded the hydrazide natural product geralcin A and dihydrogeralcin B, a saturated analog of geralcin B. Biological evaluation of the latter indicated that the presence of the enehydrazide moiety in geralcin B is critical for anticancer activity.

ChemInform Abstract: Highly Chemoselective Rauhut—Currier Reaction Between Maleimides and Enones and Dual Phosphine‐Mediated One‐Pot Synthesis of Bicyclic and Polycyclic Skeletons.

A highly chemoselective phosphine-catalyzed Rauhut–Currier reaction between maleimides and enones has been realized under very mild conditions, affording the corresponding cross-coupling products in moderate to excellent yields. On the basis of this reaction, an efficient dual phosphine-mediated one-pot synthesis of bicyclic and polycyclic compounds containing a cyclopenta[c]pyrrole skeleton has been accordingly developed, which features a tandem sequence of intermolecular Rauhut–Currier reaction and intramolecular Wittig reaction.

A Computational Study: Reactivity Difference between Phosphine- and Amine-Catalyzed Cycloadditions of Allenoates and Enones

Allenoates and enones form cyclopentenes via a phosphine-catalyzed [3 + 2] cycloaddition while the amine-catalyzed [2 + 4] cycloaddition yields dihydropyrans or pyrans. The difference between these catalysts is studied with M06-2X/6-31+G* calculations. The addition of the catalyst to the allenoate is the first step in both pathways followed by the reaction with the enone. The formation of the [3 + 2] phosphorus-ylide is exergonic, and hence, the [3 + 2] cycloaddition is kinetically favored over the [2 + 4] addition. Amines do not stabilize [3 + 2] ammonium-ylides. However, electron-withdrawing groups on the enone enable [2 + 4] cycloadditions. The strength of the electron-withdrawing group further controls the α/γ regioselectivity of the [2 + 4] cycloaddition, and the analysis of the HOMO-LUMO interactions explains why only E-dihydropyrans from the direct γ-[2 + 4] cycloaddition have been observed in experiments. The quantum calculations further reveal a new path to the α-[2 + 4] product starting with an intermediate Rauhut-Currier reaction. This new path is kinetically favored over the direct amine-catalyzed α-[2 + 4] cycloaddition.

ChemInform Abstract: Domino Cyclization Initiated by Cross‐Rauhut—Currier Reactions

AbstractReview: 87 refs.

Highly Chemoselective Rauhut–Currier Reaction between Maleimides and Enones and Dual Phosphine-Mediated One-Pot Synthesis of Bicyclic and Polycyclic Skeletons

A highly chemoselective phosphine-catalyzed Rauhut-Currier reaction between maleimides and enones has been realized under very mild conditions, affording the corresponding cross-coupling products in moderate to excellent yields. On the basis of this reaction, an efficient dual phosphine-mediated one-pot synthesis of bicyclic and polycyclic compounds containing a cyclopenta[c]pyrrole skeleton has been accordingly developed, which features a tandem sequence of intermolecular Rauhut-Currier reaction and intramolecular Wittig reaction.

The roles of counterion and water in a stereoselective cysteine-catalyzed Rauhut-Currier reaction: a challenge for computational chemistry.

The stereoselective Rauhut-Currier (RC) reaction catalyzed by a cysteine derivative has been explored computationally with density functional theory (M06-2X). Both methanethiol and a chiral cysteine derivative were studied as nucleophiles. The complete reaction pathway involves rate-determining elimination of the thiol catalyst from the Michael addition product. The stereoselective Rauhut-Currier reaction, catalyzed by a cysteine derivative as a nucleophile, has also been studied in detail. This reaction was experimentally found to be extremely sensitive to the reaction conditions, such as the number of water equivalents and the effect of potassium counterion. The E1cB process for catalyst elimination has been explored computationally for the eight possible stereoisomers. The effect of explicit water solvation and the presence of counterion (either K(+) or Na(+) ) has been studied for the lowest energy enantiomer pair (1S, 2R, 3S)/(1R, 2S, 3R).

Domino Cyclization Initiated by Cross‐Rauhut–Currier Reactions

AbstractThe Rauhut–Currier reaction has proved itself as a promising strategy for synthesis of multifunctionalized molecules, although still being in its infancy with regard to limitations of selectivity and scope. Considerable attention has thus been devoted to resolution of difficulties associated with controlling strategies and enantioselectivity. Carbocycles with distinct structural frameworks can be assembled rapidly through incorporation of cross‐Rauhut–Currier reactions into domino processes. The fine compatibility and widespread utility of Rauhut–Currier reactions is illustrated with several recent outstanding examples, with the aim of shedding light on the design of new substrates and catalysts for syntheses of complex molecules.

ChemInform Abstract: Facile Synthesis of α‐Methylidene‐γ‐butyrolactones: Intramolecular Rauhut—Currier Reaction Promoted by Chiral Acid—Base Organocatalysts.

AbstractHighly functionalized α‐methylidene‐γ‐butyrolactones are formed enantioselectively from prochiral dienone enolates in the presence of chiral organocatalysts (CHOC).

Rauhut–Currier Reaction of Nitroalkenes with Vinyl Sulfones

The Rauhut-Currier reaction between nitroalkenes and vinyl sulfones has been successfully carried out for the first time. The reaction proceeds in the presence of an imidazole/LiCl catalyst system in dioxane to provide the adducts possessing a synthetically useful 1-bis-sulfonyl-3-nitroalkene moiety in good to excellent yield. A one-pot transformation of the products to β-sulfonyl-α,β-unsaturated ketoximes has also been demonstrated.

Rhodium‐Catalyzed Asymmetric Arylative Cyclization of meso‐1,6‐Dienynes Leading to Enantioenriched cis‐Hydrobenzofurans

Chiral cis-hydrobenzofurans represent a uniquemotif existing in numerous natural products, for instance, isoambrox, haterumaimide I, rosenonolactone, incarviditone, and millingtonine A (Scheme 1a). Owing to their diverse biological activities, a great deal of attention has been paid to the development of efficient methods toward their enantioselective syntheses. One of the most straightforward and powerful ways to construct such a framework is the catalytic asymmetric desymmetrization of cyclohexadienones (Scheme 1b). In recent elegant reports, Rovis and co-workers demonstrated the feasibility of using chiral-NHC-catalyzed intramolecular Stetter reactions for the asymmetric desymmetrization of cyclohexadienones to prepare chiral cis-hydrobenzofuranones. Very recently, Sasai and co-workers described the use of bifunctional chiral phosphinothiourea catalysts in a intramolecular Rauhut–Currier reaction for the enantioselective discrimination of cyclohexadienones. Although these protocols proved to be highly effective, their efforts were mainly focused on the application of chiral organocatalysts in intramolecular reactions with a limited substrate scope. Moreover, transition metal catalyzed asymmetric desymmetrization of cyclohexadienones is quite scarce. During our continuous efforts in exploring rhodium/chiral diene-catalyzed asymmetric arylation, we envisioned that a rhodium-catalyzed tandem arylrhodation/conjugate addition reaction of cyclohexadienone-containing 1,6-dienynes, which are accessible from dearomatization of corresponding phenols, would provide a novel approach to these enantioenriched cis-hydrobenzofurans (Scheme 1c). However, two major concerns need to be addressed in this rhodium-catalyzed asymmetric desymmetrization process.

Facile synthesis of α-methylidene-γ-butyrolactones: intramolecular Rauhut–Currier reaction promoted by chiral acid–base organocatalysts

The acid–base organocatalyzed intramolecular Rauhut–Currier (RC) reaction of the dienone enolates has been developed. The enantioselective RC process produces the highly functionalized α-methylidene-γ-butyrolactones as a single diastereomer with up to 98% ee.

A Highly Nucleophilic Multifunctional Chiral Phosphane‐Catalyzed Asymmetric Intramolecular Rauhut–Currier Reaction

AbstractAn asymmetric variant of the intramolecular Rauhut–Currier (RC) reaction can be achieved using a highly nucleophilic multifunctional chiral phosphane; the corresponding cyclopentene and cyclohexene derivatives are produced in moderate to good yields and with good to excellent enantioselectivities.

ChemInform Abstract: Enantioselective Synthesis of α‐Alkylidene‐γ‐butyrolactones: Intramolecular Rauhut—Currier Reaction Promoted by Acid/Base Organocatalysts.

AbstractAn atom‐economical, chemo‐, diastereo‐, and enantioselective approach is presented.

The Intramolecular Allenolate Rauhut–Currier Reaction

An intramolecular Rauhut-Currier reaction utilizing alkynoates as the initial conjugate acceptor affords densely functionalized 5- and 6-membered rings from ynoate-enoate, ynoate-enenitrile, and alkynyl sulfone-enenitrile substrates. Trialkylphosphines catalyze the reaction, and TMSCN serves as a pronucelophile to effect turnover of the catalyst and the formation of a second C-C bond. Because of the highly electrophilic alkyne acceptor, this reaction yields products that cannot be easily accessed from the traditional Rauhut-Currier reaction.

Phosphine‐Catalyzed Rauhut–Currier Domino Reaction: A Facile Strategy for the Construction of Highly Functionalized Cyclopentene

New strategy: A novel phosphine-catalyzed domino reaction of activated conjugated dienes and electron-deficient olefins was developed. In this reaction, intermolecular Rauhut–Currier reaction was successfully incorporated in a domino process, and a variety of highly functionalized cyclopentenes were obtained in good yields and diastereoselectivities. Two new CC bonds were formed together with a quaternary carbon center.